Let’s Do Better: Public Representations of COVID-19 Science

COVID science is being both done and circulated at a furious pace. While it is inspiring to see the research community responding so vigorously to the pandemic crisis, all this activity has also created a churning sea of bad data, conflicting results, and exaggerated headlines. With representations of science becoming increasingly polarized, twisted and hyped, there is growing concern that the relevant science is being represented to the public in a manner that may cause confusion, inappropriate expectations, and the erosion of public trust. Here we explore some of the key issues associated with the representations of science in the context of the COVID-19 pandemic. Many of these issues are not new. But the COVID-19 pandemic has placed a spotlight on the biomedical research process and amplified the adverse ramifications of poor public communication. We need to do better. As such, we conclude with ten recommendations aimed at key actors involved in the communication of COVID-19 science, including government, funders, universities, publishers, media and the research communities

Consent for Nondiagnostic Research Biopsies: A Pilot Study of Participant Recall and Therapeutic Orientation

A growing number of clinical trials incorporate invasive procedures like nondiagnostic tumor biopsies for biomarker or pharmacodynamic analysis.1 Such invasive research procedures are ethically contentious. Tumor biopsies involve pain and complication risk,2 and at least one procedure-related death has been reported.3 However, nondiagnostic tumor biopsies obtained in the research context generally have no value for managing the participant’s medical condition. Some commentators therefore argue that research biopsies “take” from participants without “giving in return.”4 Because such procedures are conducted contrary to research participants’ medical interests, an ethical framework for enrolling patients in studies that include a research biopsy rides heavily on informed consent. In particular, study participants should understand that research biopsies are nontherapeutic and burdensome and that participation is discretionary in studies involving them. Yet little is known about whether decisions to enroll in a study that involves a research biopsy, including those that permit participants to opt out of the procedure, meet thresholds of consent validity, in other words, whether individuals sufficiently understand and appreciate the consequences of their decision and whether they are not unduly influenced.5 Some studies about research biopsies suggest that individuals often misconstrue nondiagnostic biopsies as therapeutic; 6 others suggest the contrary.7 Interpreting these findings is further complicated by the fact that because participants were often enrolled in clinical drug trials, they might have legitimately imputed therapeutic value to research biopsies when receiving access to investigational drugs was conditioned on providing a biopsy for research.8 There are at least three reasons that clinical trials that include research biopsies might present challenges for consent validity. First, because procedures are burdensome, individuals who enroll in these trials might do so under the mistaken belief that the biopsies provide a therapeutic benefit to them. Second, biopsies are often conducted proximate to therapeutic encounters, where patients undergoing a biopsy might be focused on a recent diagnosis and on management options, not on their role as a research participant. Last, some argue that because research participants often conflate research with clinical care,9 they might fail to appreciate the nontherapeutic nature of a research biopsy. To investigate these issues, we used semistructured interviews to probe recalled perceptions, motivations, and consent quality for research participants in a cancer biomarker study involving nondiagnostic biopsies

Consent for Nondiagnostic Research Biopsies: A Pilot Study of Participant Recall and Therapeutic Orientation

A growing number of clinical trials incorporate invasive procedures like nondiagnostic tumor biopsies for biomarker or pharmacodynamic analysis.1 Such invasive research procedures are ethically contentious. Tumor biopsies involve pain and complication risk,2 and at least one procedure-related death has been reported.3 However, nondiagnostic tumor biopsies obtained in the research context generally have no value for managing the participant’s medical condition. Some commentators therefore argue that research biopsies “take” from participants without “giving in return.”4 Because such procedures are conducted contrary to research participants’ medical interests, an ethical framework for enrolling patients in studies that include a research biopsy rides heavily on informed consent. In particular, study participants should understand that research biopsies are nontherapeutic and burdensome and that participation is discretionary in studies involving them. Yet little is known about whether decisions to enroll in a study that involves a research biopsy, including those that permit participants to opt out of the procedure, meet thresholds of consent validity, in other words, whether individuals sufficiently understand and appreciate the consequences of their decision and whether they are not unduly influenced.5 Some studies about research biopsies suggest that individuals often misconstrue nondiagnostic biopsies as therapeutic; 6 others suggest the contrary.7 Interpreting these findings is further complicated by the fact that because participants were often enrolled in clinical drug trials, they might have legitimately imputed therapeutic value to research biopsies when receiving access to investigational drugs was conditioned on providing a biopsy for research.8 There are at least three reasons that clinical trials that include research biopsies might present challenges for consent validity. First, because procedures are burdensome, individuals who enroll in these trials might do so under the mistaken belief that the biopsies provide a therapeutic benefit to them. Second, biopsies are often conducted proximate to therapeutic encounters, where patients undergoing a biopsy might be focused on a recent diagnosis and on management options, not on their role as a research participant. Last, some argue that because research participants often conflate research with clinical care,9 they might fail to appreciate the nontherapeutic nature of a research biopsy. To investigate these issues, we used semistructured interviews to probe recalled perceptions, motivations, and consent quality for research participants in a cancer biomarker study involving nondiagnostic biopsies

Consent for Nondiagnostic Research Biopsies: A Pilot Study of Participant Recall and Therapeutic Orientation

A growing number of clinical trials incorporate invasive procedures like nondiagnostic tumor biopsies for biomarker or pharmacodynamic analysis.1 Such invasive research procedures are ethically contentious. Tumor biopsies involve pain and complication risk,2 and at least one procedure-related death has been reported.3 However, nondiagnostic tumor biopsies obtained in the research context generally have no value for managing the participant’s medical condition. Some commentators therefore argue that research biopsies “take” from participants without “giving in return.”4 Because such procedures are conducted contrary to research participants’ medical interests, an ethical framework for enrolling patients in studies that include a research biopsy rides heavily on informed consent. In particular, study participants should understand that research biopsies are nontherapeutic and burdensome and that participation is discretionary in studies involving them. Yet little is known about whether decisions to enroll in a study that involves a research biopsy, including those that permit participants to opt out of the procedure, meet thresholds of consent validity, in other words, whether individuals sufficiently understand and appreciate the consequences of their decision and whether they are not unduly influenced.5 Some studies about research biopsies suggest that individuals often misconstrue nondiagnostic biopsies as therapeutic; 6 others suggest the contrary.7 Interpreting these findings is further complicated by the fact that because participants were often enrolled in clinical drug trials, they might have legitimately imputed therapeutic value to research biopsies when receiving access to investigational drugs was conditioned on providing a biopsy for research.8 There are at least three reasons that clinical trials that include research biopsies might present challenges for consent validity. First, because procedures are burdensome, individuals who enroll in these trials might do so under the mistaken belief that the biopsies provide a therapeutic benefit to them. Second, biopsies are often conducted proximate to therapeutic encounters, where patients undergoing a biopsy might be focused on a recent diagnosis and on management options, not on their role as a research participant. Last, some argue that because research participants often conflate research with clinical care,9 they might fail to appreciate the nontherapeutic nature of a research biopsy. To investigate these issues, we used semistructured interviews to probe recalled perceptions, motivations, and consent quality for research participants in a cancer biomarker study involving nondiagnostic biopsies

Patient-Funded Trials: Opportunity or Liability?

Patient-funded trials are gaining traction as a means of accelerating clinical translation. However, such trials sidestep mechanisms that promote rigor, relevance, efficiency, and fairness. We recommend that funding bodies or research institutions establish mechanisms for merit review of patient-funded trials, and we offer some basic criteria for evaluating PFT protocol

Clinical development success rates and social value of pediatric Phase 1 trials in oncology

ObjectivesDrug development trials must fulfill social value requirement but no estimates of value provided by pediatric Phase 1 trials in oncology exist. These trials involve a particularly vulnerable population. Our objective was to assess of surrogates of social value of Phase 1 trials performed in pediatric oncology: rates of approval of tested interventions, transition to further phases of testing and citation in subsequent primary research reports.MethodsWe performed an analysis on a subset of eligible trials included in a previous meta-analysis. That study systematically searched EMBASE and PubMed for small sample size, non-randomized, dose escalation pediatric cancer Phase 1 studies of any malignancy, assessing chemotherapy and/or targeted therapy and looked at risk and benefit. The current analysis assessed all studies in that review published between January 1st 2004 and December 31st 2013 for predictors of social value. This time range allowed for at least five years of subsequent development activity. Sources of data included FDA and EMA medicine databases (for approval), ClinicalTrials.gov and EU Clinical Trials Register (for transition) and Google Scholar (for citation).ResultsOne hundred thirty-nine trials enrolling 3814 patients met the eligibility criteria. Seven trials (5%) led to drugs being registered for pediatric use in therapy of cancer. Fifty-two (37%) transitioned to later phases of pediatric oncology trials according to ClinicalTrials.gov and/or EU Register. Over 90% of trials were cited by at least one subsequent primary research report or systematic review. Most of the citations were preclinical studies.ConclusionsOur analysis shows that treatments tested in pediatric Phase 1 trials in oncology have low rates of regulatory approval. However, a large proportion of Phase 1 trials inform further testing and development of tested interventions

Can patient decision aids help people make good decisions about participating in clinical trials? A study protocol

<p>Abstract</p> <p>Background</p> <p>Evidence shows that the standard process for obtaining informed consent in clinical trials can be inadequate, with study participants frequently not understanding even basic information fundamental to giving informed consent. Patient decision aids are effective decision support tools originally designed to help patients make difficult treatment or screening decisions. We propose that incorporating decision aids into the informed consent process will improve the extent to which participants make decisions that are informed and consistent with their preferences. A mixed methods study will test this proposal.</p> <p>Methods</p> <p>Phase one of this project will involve assessment of a stratified random sample of 50 consent documents from recently completed investigator-initiated clinical trials, according to existing standards for supporting good decision making. Phase two will involve interviews of a purposive sample of 50 trial participants (10 participants from each of five different clinical areas) about their experience of the informed consent process, and how it could be improved. In phase three, we will convert consent forms for two completed clinical trials into decision aids and pilot test these new tools using a user-centered design approach, an iterative development process commonly employed in computer usability literature. In phase four, we will conduct a pilot observational study comparing the new tools to standard consent forms, with potential recruits to two hypothetical clinical trials. Outcomes will include knowledge of key aspects of the decision, knowledge of the probabilities of different outcomes, decisional conflict, the hypothetical participation decision, and qualitative impressions of the experience.</p> <p>Discussion</p> <p>This work will provide initial evidence about whether a patient decision aid can improve the informed consent process. The larger goal of this work is to examine whether study recruitment can be improved from (barely) informed consent based on disclosure-oriented documents, towards a process of high-quality participant decision-making.</p

Faisons mieux les choses : représentation publique de la science sur la COVID-19

Les recherches scientifiques sur la COVID-19 sont à la fois menées et diffusées à une cadence effrénée. Bien qu’il soit inspirant de voir la communauté de la recherche répondre avec autant de vigueur à la crise causée par la pandémie, toute cette activité a par ailleurs engendré un chaos de mauvaises données, de résultats contradictoires et de manchettes exagérées. Alors que la polarisation, la déformation et la médiatisation des résultats scientifiques s’intensifient chaque jour, les inquiétudes se font de plus en plus sentir quant à la perspective que la science pertinente soit présentée au public d’une manière qui puisse causer de la confusion, créer de fausses attentes et éroder la confiance du public. Dans cette note, nous explorons les principaux enjeux associés à la présentation de la science dans le contexte de la pandémie de la COVID-19. Plusieurs de ces enjeux ne sont pas nouveaux. Mais la pandémie de la COVID-19 a braqué les projecteurs sur le processus de la recherche biomédicale et a amplifié les ramifications néfastes des problèmes de communication publique. Nous devons faire mieux. À ce titre, nous conclurons ce rapport en formulant dix recommandations qui s’adressent aux acteurs clés qui interviennent dans la communication de la science sur la COVID-19, notamment les gouvernements, les bailleurs de fonds, les universités, les éditeurs, les médias et les communautés de recherche

Forecasts for the Attainment of Major Research Milestones in Parkinson's Disease.

BACKGROUND: Projections about when research milestones will be attained are often of interest to patients and can help inform decisions about research funding and health system planning. OBJECTIVE: To collect aggregated expert forecasts on the attainment of 11 major research milestones in Parkinson's disease (PD). METHODS: Experts were asked to provide predictions about the attainment of 11 milestones in PD research in an online survey. PD experts were identified from: 1) The Michael J. Fox Foundation for Parkinson's Research data base, 2) doctors specializing in PD at top ranked neurology centers in the US and Canada, and 3) corresponding authors of articles on PD in top medical journals. Judgments were aggregated using coherence weighting. We tested the relationship between demographic variables and individual judgments using a linear regression. RESULTS: 249 PD experts completed the survey. In the aggregate, experts believed that new treatments like gene therapy for monogenic PD, immunotherapy and cell therapy had 56.1%, 59.7%, and 66.6% probability, respectively of progressing in the clinical approval process within the next 10 years. Milestones involving existing management approaches, like the approval of a deep brain stimulation device or a body worn sensor had 78.4% and 82.2% probability of occurring within the next 10 years. Demographic factors were unable to explain deviations from the aggregate forecast (R2 = 0.029). CONCLUSIONS: Aggregated expert opinion suggests that milestones for the advancement of new treatment options for PD are still many years away. However, other improvements in PD diagnosis and management are believed to be near at hand

Comparison of Patient and Expert Perceptions of the Attainment of Research Milestones in Parkinson's Disease.

BACKGROUND: Commentators suggest that patients have unrealistic expectations about the pace of research advances and that such expectations interfere with patient decision-making. OBJECTIVE: The objective of this study was to compare expert expectations about the timing of research milestone attainment with those of patients who follow Parkinson's disease (PD) research. METHODS: Patients with PD and experts were asked to provide forecasts about 11 milestones in PD research in an online survey. PD experts were identified from a Michael J. Fox Foundation database, highly ranked neurology centers in the United States and Canada, and corresponding authors of articles on PD in top medical journals. Patients with PD were recruited through the Michael J. Fox Foundation. We tested whether patient forecasts differed on average from expert forecasts. We also tested whether differences between patient forecasts and the average expert forecasts were associated with any demographic factors. RESULTS: A total of 256 patients and 249 PD experts completed the survey. For 9 of the 11 milestones, patients' forecasts were on average higher than those of experts. Only exercise therapy met our 10% difference threshold for practical significance. Education was the only demographic that predicted patient deviations from expert forecasts on milestone forecasts. Patients offered significantly higher forecasts than experts that the clinical trials used in milestone queries would report positive primary outcomes. CONCLUSIONS: Differences between patient and expert expectations about research milestones were generally minor, suggesting that there is little cause for concern that patients who follow PD research are unduly swayed by inaccurate representations of research advancement in the media or elsewhere. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society